Keeping Cholesterol Under Control

Cholesterol is the Jekyll and Hyde of the body. Like the literary split personality, it has a good side because it is needed for certain important body functions. But for many Americans, cholesterol also has an evil side. When present in excessive amounts, it can injure blood vessels
and cause heart attacks and stroke.

The body needs cholesterol for digesting dietary fats, making hormones,
building cell walls, and other important processes. The bloodstream carries
cholesterol in particles called lipoproteins that are like blood-borne cargo
trucks delivering cholesterol to various body tissues to be used, stored or
excreted. But too much of this circulating cholesterol can injure arteries,
especially the coronary ones that supply the heart. This leads to accumulation
of cholesterol-laden "plaque" in vessel linings, a condition called
atherosclerosis.

When blood flow to the heart is impeded, the heart muscle becomes starved for
oxygen, causing chest pain (angina). If a blood clot completely obstructs a
coronary artery affected by atherosclerosis, a heart attack (myocardial
infarction) or death can occur.

Heart disease is the number one killer of both men and women in this country.
More than 90 million American adults, or about 50 percent, have elevated blood
cholesterol levels, one of the key risk factors for heart disease, according to
the National Heart, Lung, and Blood Institute's National Cholesterol Education
Program.

While the institute estimates that heart disease killed nearly half a million
in 1996, the most recent year for which figures are available, a study published
in the New England Journal of Medicine in September 1998 says heart disease
deaths have declined steadily over the last 30 years. Indeed, between 1990 and
1994, heart disease deaths decreased by 10.3 percent, the study says. From this
and other studies, it appears that this is due largely to improvements in
medical care after heart attack, a reduction in the number of repeat heart
attacks, and better prevention of heart disease development.

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A key factor in this drop is that the public, patients and doctors today are
better informed about the risks associated with elevated cholesterol and the
benefits of lifestyle changes and medical measures aimed at lowering blood
cholesterol. "Public health initiatives such as the National Cholesterol
Education Program have raised consumer awareness, promoted effective
interventions, and have likely contributed to the reduction in heart disease
deaths," says David Orloff, M.D., of the Food and Drug Administration's division
of metabolic and endocrine drug products.

Another factor in the drop may be a relatively new class of drugs called
statins. These have provided doctors with an arsenal of therapies to lower
elevated blood cholesterol levels, often dramatically. To date, FDA has approved
six statin drugs.

When Blood Cholesterol Becomes a Problem

Two types of lipoproteins and their quantity in the blood are main factors in
heart disease risk:

Low-density lipoprotein (LDL)--This "bad" cholesterol is the form in which
cholesterol is carried into the blood and is the main cause of harmful fatty
buildup in arteries. The higher the LDL cholesterol level in the blood, the
greater the heart disease risk.

One of the primary ways LDL cholesterol levels can become too high in blood
is through eating too much of two nutrients: saturated fat, which is found
mostly in animal products, and cholesterol, found only in animal products.
Saturated fat raises LDL levels more than anything else in the diet (see "Food for Thought").

Several other factors also affect blood cholesterol levels:

Heredity--High cholesterol often runs in families. Even though specific
genetic causes have been identified in only a minority of cases, genes still
play a role in influencing blood cholesterol levels.

Exercise--Regular physical activity may not only lower LDL cholesterol,
but it may increase levels of desirable HDL.

Age and gender--Before menopause, women tend to have total cholesterol
levels lower than men at the same age. Cholesterol levels naturally rise as
men and women age. Menopause is often associated with increases in LDL
cholesterol in women.

Stress--Studies have not shown stress to be directly linked to cholesterol
levels. But experts say that because people sometimes eat fatty foods to
console themselves when under stress, this can cause higher blood
cholesterol.

Though high total and LDL cholesterol levels, along with low HDL cholesterol,
can increase heart disease risk, they are among several other risk factors.
These include cigarette smoking, high blood pressure, diabetes, obesity, and
physical inactivity. If any of these is present in addition to high blood
cholesterol, the risk of heart disease is even greater.

The good news is that all these can be brought under control either by
changes in lifestyle--such as diet, losing weight, or an exercise program--or
quitting a tobacco habit. Drugs also may be necessary in some people. Sometimes
one change can help bring several risk factors under control. For example,
weight loss can reduce blood cholesterol levels, help control diabetes, and
lower high blood pressure.

But some risk factors cannot be controlled. These include age (45 years or
older for men and 55 years or older for women) and family history of early heart
disease (father or brother stricken before age 55; mother or sister stricken
before age 65).

What Is High Blood Cholesterol?

Cholesterol levels are determined through chemical analysis of a blood sample
taken from a finger prick or from a vein in the arm. Home cholesterol kits,
first approved in 1993, test only for total cholesterol levels but are as
accurate as tests done in a doctor's office, says Steven Gutman, M.D., director
of FDA's division of clinical laboratory devices. "These tests can give a
consumer very valuable information when screening for high cholesterol," he
says. "But they shouldn't be considered substitutes for a test conducted in a
doctor's office." He adds that if test results are elevated, consumers should
see a doctor right away for a more refined blood analysis. The National
Cholesterol Education Program considers cholesterol testing in a doctor's office
to be the preferred way because the patient can get advice immediately about the
meaning of the results and what to do.

Besides determining total cholesterol levels, doctors often order a
lipoprotein profile that shows the amounts of LDL, HDL, and another type of
blood fat called triglycerides. This information gives doctors a better idea of
heart disease risk and helps guide any treatment.

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Cholesterol levels are measured in milligrams per deciliter (mg/dL). The
National Cholesterol Education Program developed the following classifications
for people over age 20 who do not have heart disease:

Desirable blood cholesterol--Total blood cholesterol is less than 200
mg/dL; LDL is lower than 130 mg/dL.

Borderline high cholesterol--Total level is between 200 and 239 mg/dL or
LDL is 130 to 159 mg/dL.

High blood cholesterol--Total level is greater than 240 mg/dL or LDL is
160 mg/dL or higher. For patients with heart disease, LDL above 100 mg/dL is
too high. In addition, an HDL level less than 35 mg/dL is considered low and
increases the risk of heart disease.

The main goal of cholesterol treatment is to lower LDL in people without
heart disease. If the LDL level is in the "high" category and fewer than two
other risk factors for heart disease are present, the goal is an LDL level lower
than 160 mg/dL. If two or more risk factors are present, the goal is less than
130 mg/dL. If a patient already has heart disease, LDL levels should be 100
mg/dL or less. By reducing LDL, heart disease patients may prevent future heart
attacks, prolong their lives, and slow down or even reverse cholesterol buildup
in the arteries, according to the National Heart, Lung, and Blood Institute.

Treating High Blood Cholesterol

When a patient without heart disease is first diagnosed with elevated blood
cholesterol, doctors often prescribe a program of diet, exercise, and weight
loss to bring levels down. National Cholesterol Education Program guidelines
suggest at least a six-month program of reduced dietary saturated fat and
cholesterol, together with physical activity and weight control, as the primary
treatment before resorting to drug therapy. Typically, doctors prescribe the
Step I/Step II diet (see "Food for Thought") to lower dietary fat, especially
saturated fat. Many patients respond well to this diet and end up sufficiently
reducing blood cholesterol levels. Study data reinforce these benefits. For
example, a 1998 Columbia University study examined 103 male and female patients
of diverse ages and ethnic backgrounds and found that reducing dietary saturated
fat directly affected blood cholesterol. For every 1 percent drop in saturated
fat, the study showed a 1 percent lowering of LDL in patients.

But sometimes diet and exercise alone are not enough to reduce cholesterol to
goal levels. Perhaps a patient is genetically predisposed to high blood
cholesterol. In these cases, doctors often prescribe drugs. The National
Cholesterol Education Program estimates that as many as 9 million Americans take
some form of cholesterol-lowering drug therapy. The most prominent cholesterol
drugs are in the statin family, an array of powerful treatments that includes
Mevacor (lovastatin), Lescol (fluvastatin), Pravachol (pravastatin), Zocor
(simvastatin), Baycol (cervastatin), and Lipitor (atorvastatin). Many doctors
say statin drugs have revolutionized patient care.

"These drugs have had a fantastic impact on cholesterol treatment," says
Redonda Miller, M.D., assistant professor of medicine at Johns Hopkins
University School of Medicine. "They all lower cholesterol levels, but the side
effects are minimal."

A study published in the medical journal Circulation in 1998 showed that
statins dramatically lower the risk of dying from heart disease. Research found
that for every 10 percentage points cholesterol was reduced, the risk of death
from heart disease dropped by 15 percent.

So far, only three of the drugs--Mevacor, Zocor and Pravachol--have been
studied in long-term, controlled trials. "Based on existing evidence, [statin
drugs] all have similar safety profiles and are effective at lowering
cholesterol in appropriately selected patients," says FDA's Orloff. "The
difference between drugs lies mainly in their absolute capacity to lower
cholesterol--that is, at the highest approved daily doses."

One landmark study completed in 1994, the Scandinavian Simvastatin Survival
Study, or 4S, showed a 42 percent reduction in deaths from heart disease and a
30 percent drop in death from all causes over five years in patients with
coronary heart disease whose high LDL levels were lowered with Zocor. The West
of Scotland study, reported in 1995, revealed similar benefits from lowering LDL
levels with Pravachol in patients without heart disease. And the Cholesterol and
Recurrent Events (CARE) study, reported in 1996, showed that lowering LDL levels
with Pravachol reduced heart attacks and deaths in patients with a previous
heart attack but with cholesterol levels relatively average for the general
population. This study showed that Pravachol treatment not only reduced death
from heart disease but also death from all causes in a group of heart disease
patients with average cholesterol levels.

A 1997 study, the Air Force/Texas Coronary Atherosclerosis Prevention Study,
showed that Mevacor helped prevent a first heart attack or unstable angina in
men and women with average cholesterol levels but with below-average HDL.

Statins work by interfering with the cholesterol-producing mechanisms of the
liver and by increasing the capacity of the liver to remove cholesterol from
circulating blood. Statins can lower LDL cholesterol by as much as 60 percent,
depending on the drug and dosage.

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Heart patient Norbert Hoffmann, 65, of Northfield, Minn., saw what he calls
"a dramatic drop" in cholesterol levels after taking Zocor for three months. For
example, his total cholesterol went from 270 to 145 mg/dL and LDL from 182 to 82
mg/dL.

But patients can respond differently to drugs. Some patients may have fewer
side effects with one drug than another. "I had problems such as stomach cramps
with Zocor," says Oklahoma patient Linden Gilbert, 50. His doctor ultimately
switched him to Lipitor, which he credits with lowering his total cholesterol
from 230 to 150 mg/dL.

Other Drug Treatments

These include:

Nicotinic acid (niacin)-This lowers total and LDL cholesterol and raises
HDL cholesterol. It also can lower triglycerides. Because the dose needed for
treatment is about 100 times more than the Recommended Daily Allowance for
niacin and thus can potentially be toxic, the drug must be taken under a
doctor's care.

Resins--Doctors have been prescribing Questran (cholestyramine) and
Colestid (colestipol) for about 20 years. These "resins" bind bile acids in
the intestine and prevent their recycling through the liver. Because the liver
needs cholesterol to make bile, it increases its uptake of cholesterol from
the blood.

Aspirin--Because studies have shown that aspirin can have a protective
effect against heart attacks in patients with clogged blood vessels, doctors
often prescribe the drug to patients with heart disease.

The decision of which drug to prescribe is one the doctor makes based on
factors such as degree of cholesterol lowering desired, side effects, and cost.
"If a patient has only a modest cholesterol elevation, I might prescribe
Mevacor," says Johns Hopkins' Miller. "But if a more drastic reduction is
needed, especially of LDL, I'll prescribe Lipitor."

The potential for drug interaction is a crucial concern, says FDA's Orloff.
"Some statin drugs are known to interact adversely with other drugs, and that
information may guide a decision about which statin to use." In June 1998, FDA
announced the withdrawal of the drug Posicor (mibefradil), used to treat high
blood pressure and stable angina, because it caused adverse reactions in
patients taking various other drugs, including Mevacor and Zocor.

Though it is impossible to know yet just how many lives cholesterol-lowering
therapies have saved, public health experts say awareness efforts such as the
National Cholesterol Education Program are getting the word out to Americans
about heart disease, its prevention and management. Reflecting on his own
experience with elevated cholesterol, Hoffmann says, "Get informed [about
cholesterol]. Read books, search the Internet, look at your risk factors, and,
most of all, don't wait to do something about it if you have a [cholesterol]
problem."

Food for Thought

One of the main ways blood cholesterol can reach undesirable levels is
through a diet high in saturated fat and cholesterol. Fatty cholesterol deposits
can collect in blood vessels, raising the risk of heart disease.

Drugs, exercise, and other therapies may be prescribed. But in many cases,
cholesterol levels can be lowered by revising dietary habits and limiting the
kinds of foods known to boost cholesterol, such as those high in saturated fat.
This doesn't mean totally eliminating all your favorite foods, such as desserts,
says the National Cholesterol Education Program (NCEP). It means taking a more
prudent approach to the kinds and amounts of foods you eat.

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When elevated cholesterol is first discovered in a person without heart
disease, doctors often start patients on the Step I diet recommended by the
American Heart Association and NCEP. On this program, patients should eat: 8 to
10 percent of the day's total calories from saturated fat, 30 percent or less of
total calories from fat, less than 300 milligrams of dietary cholesterol a day,
and just enough calories to achieve and maintain a healthy weight. A doctor or a
registered dietitian can suggest a reasonable calorie level. Food labels also
are very helpful in determining how much saturated fat, cholesterol, and
calories are in various foods.

If the Step I diet doesn't result in desirable cholesterol levels, doctors
may try the Step II diet, which changes the daily saturated fat limits to below
7 percent of daily calories and dietary cholesterol to below 200 milligrams.
Step II also is the diet for people with heart disease.

In many patients, blood cholesterol levels should begin to drop a few weeks
after starting on a cholesterol-lowering diet. Just how much of a drop depends
on factors such as how high the cholesterol level is and how each person's body
responds to changes made. With time, cholesterol levels may be reduced 10 to 50
milligrams per deciliter or more, a clinically significant amount.

For more information on lowering blood cholesterol through diet or other
means, contact: